We propose to continue and extend our studies on molecular events leading to poliovirus replication and our analysis of neutralization antigenic sites of the virus particle. Specifically, we propose to analyze the structure and function(s) of the 5' non- coding region of poliovirus RNA, to determine processes of protein modification and of proteolytic cleavage of the poliovirus polyprotein, to investigate the structure and substrate recognition of the two virus-encoded proteinases, and to analyze components of viral RNA replication and the mechanism of initiation of viral RNA synthesis. Moreover, we will alter the surface structure of the poliovirion to achieve hybrid virus expressing foreign antigenic determinants in addition to those of poliovirus Type 1 (Mahoney). Our studies may lead to the development of new vaccines and of novel drugs directed against picornavirus infection.